The purpose of this project is to evaluate the utility of an intravenous microbubble-based ultrasound (US) contrast to assess the intracranial (IC) circulation and brain parenchyma before and after thrombolytic therapy. The motivation for this work is to introduce imaging end-points at the bedside to rapidly affect patient management where effective treatment must be initiated rapidly to achieve a successful outcome. Our group has been instrumental in the development of potent US contrast media and contrast specific imaging instrumentation to produce angiographic images of vessels and to increase detection of tumors and infarction in solid organs. Early work from other groups suggests that it may be possible to image brain parenchyma to detect perfusion defects. This proposal combines the expertise of our US contrast team with that of the UCSD Stroke team to implement, optimize, and evaluate this new technique in acute stroke. We propose 5 studies that will helps us validate and translate vascular and parenchymal US brain imaging into clinical practice. We will 1) Validate IC contrast-enhanced (CE) US vascular imaging in general patients scheduled for IC DSA with or without intervention planned since all will have a truth standard. 2) Validate IC CE-US vascular imaging in stroke patients whether or not they receive tPA using MRI, DSA, CT, and clinical status as truth standards. We will acquire serial studies and assess IC vessel patency. We will also assess the prognostic significance of recanalizaUon or persistent occlusion in the macro- and microvasculature. 3) Implement, optimize and validate parenchymal imaging and define the gold standard for Study #4 in a dog model that will provide a wide range of infarct sizes; 4) Validate and assess vascular and parenchymal imaging in stroke patients receiving tPA and correlate the status of vascular patency to the clinical status. We believe that direct visualization of IC vascular patency is a more powerful tool to guide Imanagement than clinical status. Two benefit from knowing the status of the IC macro- and microvessels can be exploited. Based on data from Studies 2 and 4 that related IC vascular patency to clinical status and outcome, we will develop 2 phase I protocols that stratify patients based on their vascular status to a) treat (tPA or placebo) if vascular abnormalities exist at admission in patients with mild or rapidly changing clinical status and 2) treat (aspirin, heparin, placebo) patients following tPA if they recanalize to prevent re-occlusion.